Melphalan resistant L1210 cells were also resistant to the cytotoxic action of the poorly permeable mercurial, p-chloromercuribenzenesulfonate. This cytotoxic resistance was reflected in resistance to membrane damage by the mercurial indicated by increased Na+ and Ca++ permeability and to cell swelling and lysis. The implication of an exofacial sulfhydryl group in these interactions is apparent, and it is suggested that this group is either less active or less accessible in the resistant cell.